An interesting study showing how butyrate, a product of fermentable fiber when processed by colonic bacteria, induces apoptosis especially in colon cancer cells especially when taken with fish oil.
http://jn.nutrition..../full/134/2/479
Eat that oatmeal and fish oil.Mechanisms by which the combination of fish oil and pectin (a high butyrate producer) may protect against colon tumorigenesis.
Cox-2 is inducibly expressed in tumor tissue. For example Cox-2 mRNA levels are markedly increased in 86% of human colorectal cancers (36). In turn, Cox-2 expression has been shown to downregulate apoptosis (37). When Tsujii and DuBois overexpressed Cox-2 in rat intestinal epithelial cells, those cells were resistant to butyrate-induced apoptosis (37). We have shown that Cox-2 expression is downregulated with fish oil feeding in rat colon cells (34) compared to providing corn oil in the diet (38).
A second mechanism by which the combination of fish oil and pectin may initiate apoptosis may involve production of reactive oxygen species. The mitochondria are considered the central executioners of apoptosis. We hypothesized that the fatty acids from fish oil would incorporate into the mitochondrial membrane and because they are highly unsaturated could be targets for reactive oxygen species generated as a normal part of the electron transport process. This in turn could trigger additional ROS leading to a decrease in mitochondrial membrane potential, release of cytochrome C into the cytosol and activation of caspase 3, initating apoptosis. To test this hypothesis rats were provided with diets high in fish oil or corn oil (15% by weight), and measurements made of the fatty acid composition of mitochondrial phospholipids, reactive oxygen species, translocation of cytochrome C, and activation of caspase 3. We report that fatty acids from the fish oil diet did incorporate into mitochondrial phospholipids, thus increasing the unsaturation index; in the presence of butyrate, cytochrome C translocated to the mitochondria, and caspase 3 activity was upregulated (39). Interestingly, the mechanism appears to be an increase in reactive oxygen species with fish oil feeding (40). Recently we separated the effects of butyrate production from the fiber source by providing rats with slow-release butyrate pellets and evaluating their effect on aberrant crypt formation (41). In the absence of butyrate administration, corn oil and fish oil feeding resulted in similar numbers of high multiplicity aberrant crypts/rat. In stark contrast, when butyrate was administered there were 5 times as many aberrant crypts/rat in the corn oil group compared to rats receiving fish oil (P < 0.0006) (41). This finding lends further support to our previous studies showing that the type of fat determines the efficacy of the fiber.
Edited by lucid, 08 July 2007 - 09:00 AM.
